Your environmental monitoring (EM) program must demonstrate control over both viable and non-viable particles found in critical areas of your operation. The procedures and protocols you have in place must ensure asepticism throughout your operation.
There are many complex ways of classifying your operation as aseptic. The methods used to reach a contamination-free environment, regardless of your industry or the size of your business, remain the same. These methods assist you with proving cleanliness, which is paramount when you are creating, testing or packaging medicines or substances destined for human contact or consumption.
The EU’s Good Manufacturing Practice (GMP) regulations provide for systems that ensure processes and facilities are controlled and maintained for identity, quality, purity and strength. This means EM programs need to adhere to what the EU GMP outlines as best practice. The draft of EU GMP Annex 1 reaches further, to ensure patient and human safety through the implementation of stringent guidelines.
But what is the best way to make sure you achieve and maintain these high standards?
Selecting the right environmental monitoring methods for you
Understanding exactly what to clean and monitor and where to focus these efforts is the starting point to maintaining your cleanroom. There are viable and non-viable particles that can exist in the cleanroom environment. Monitoring for both is important in understanding the asepsis of your cleanroom and operation.
Testing for the detection of viable particles includes methods for isolating bacteria, yeast and mould in your facility. You need to monitor the air, your staff and the surface areas for any microbial contamination.
The non-viable particles that do not contain any living organisms are spreading the viable particles throughout your facility, so monitoring for these is critical to maintaining asepsis. You will need to sample the air for these particles using a selected volume of air.
It is not enough to sample from anywhere. Specific areas in your cleanroom facility must be sampled to ensure you meet the quality standards, as indicated by the EU GMP Annex 1 draft revision.
The critical areas to monitor are:
Personnel working in your cleanroom
People are the most significant source of contamination within your cleanroom facility. It is common practice to have a specific routine that each staff member entering the cleanroom must adhere to. This can include doubling up on personal protective equipment (PPE) and your gowning routine, and ensuring minimal skin contact with the products, cleanroom environment or facility.
Your active cleanroom surfaces
When monitoring your surfaces, include floors, walls and equipment. All these areas must be monitored and cleaned appropriately and regularly. Typically, you should monitor regularly for viable particle counts through the use of contact plates that soon let you know about contaminants, as bacterial growth could be present.
The air in your cleanroom facility
Of course, the air in the facility will be continuously controlled by HVAC control systems. Parameters such as pressure, temperature and humidity may be continuously monitored, whereas monitoring for both viable and non-viable particle counts will be routinely carried out depending on grade of room and operations. Your air samplers for both viable and non-viable particle monitoring must be maintained and calibrated regularly, to ensure accuracy of data.
What are the most effective methods of environmental monitoring in a cleanroom facility?
Air sampling using air samplers and settle plates
Air samplers draw in a specific volume of air, that gets passed over a media plate. This plate is incubated and will reveal viable organisms and indicate the number of particles per cubic feet or litre.
Settle plates are considered the standard passive air sampling method and it makes use of Petri dishes that contain sterile growth media (Tryptic Soy Agar). These plates are left exposed in the environment. They can be left exposed in your facility for up to four hours before their integrity becomes questionable. Care should be taken when siting the settle plate as they can be easily damaged or moved. Devices such as settle plate stands can help reduce these risks as well as ensuring they are exposed at an appropriate height, for example at working height away from the work surface.
The viable particles in the air will settle onto the plates and present after incubation. Accurately measuring the contamination in the air is near impossible with this form of passive air sampling. Therefore, it is recommended that you make use of a combined monitoring program that includes both passive and active air sampling.
Surface monitoring requires two methods of environmental monitoring for best results
Contact plates are used for surface monitoring, by preparing the culture media so it protrudes above the sides of the dish. The plate is then pressed against the surface that you are attempting to sample and monitor, and any contaminants will stick to the media and present after incubation. Standardisation of this method can be achieved by using devices such Contact Plate applicators.
The second method of sampling and monitoring on surfaces is the use of sterile swabs. These are rubbed over the focus area before being transferred to the laboratory. The presence of microorganisms can then be established through the subculturing of any collected particles the swab picked up, onto culture media. This is common practice if the surface area you are trying to sample is not flat or is difficult to get to.
To monitor your personnel in your cleanroom facility you must make use of contact plates together with the correct gowning routine
To evaluate how effective your gowning program is, you can monitor your personnel by employing contact plates to assess any microbial contamination. The contact plates are used to monitor the areas of the body that might be in contact with the sterile areas of your facility. And as mentioned above, the contact plates then present any bacteria post incubation. This is a good indication of how well your staff are adhering to the gowning program you have implemented.
A vigorous and stringent environmental monitoring program provides you with critical data that helps you prevent possible contaminations in the future. It is essential to ensure compliance with the latest standards and drives your productivity going forward, with a far reduced possibility of having to stop production through contamination.